Toll-like receptor 2 activation by lipoteichoic acid induces differential production of pro-inflammatory cytokines in human odontoblasts, dental pulp fibroblasts and immature dendritic cells
Toll-like receptor 2 activation by lipoteichoic acid induces differential production of pro-inflammatory cytokines in human odontoblasts, dental pulp fibroblasts and immature dendritic cells
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DOI：
10.1016/j.imbio.2009.01.009
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发表时间：
2010-01-01
期刊：
影响因子：
2.8
通讯作者：
Farges, Jean-Christophe
中科院分区：
文献类型：
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作者：
Keller, Jean-Francois;Carrouel, Florence;Farges, Jean-Christophe
成牙本质细胞、牙髓成纤维细胞和未成熟树突状细胞（dendritic cells，DC）参与了人牙髓对龋病过程中侵入牙本质的口腔病原体的免疫应答。然而，它们如何调节革兰氏阳性菌的炎症反应仍然在很大程度上是未知的。在这项研究中，我们研究了促炎细胞因子肿瘤坏死因子-α（TNF-α），白细胞介素-1 β（1 L-1 β）和白细胞介素-8（CXCL 8）在这三种细胞类型的刺激后，与脂磷壁酸（LTA），革兰氏阳性菌的细胞壁成分，激活模式识别分子Toll样受体2（TLR 2）。我们观察到TNF-α基因表达在所有LTA刺激的细胞类型中上调。IL-1 β基因在成牙本质细胞样细胞和牙髓成纤维细胞中的表达在刺激或不刺激时均不表达或几乎不表达，但在未成熟的DC中表达，并在刺激时表达增加。TNF-α和IL-1 β蛋白在DC培养上清中检测到，而在成牙本质细胞样细胞和牙髓成纤维细胞中未检测到。LTA刺激后，CXCL 8基因和蛋白在三种细胞类型中明显表达并增加。这些数据表明，在成牙本质细胞和牙髓成纤维细胞中，与未成熟的DC相反，LTA依赖性TLR 2活化不会导致显著的TNF-α和IL-1 β产生，但是所有三种细胞类型通过CXCL 8合成和分泌影响牙髓炎症/免疫应答。(C)2009年Elsevier GmbH。All rights reserved.
Odontoblasts, dental pulp fibroblasts and immature dendritic cells (DCs) have been involved in the human dental pulp immune response to oral pathogens that invade dentine during the caries process. How they regulate the inflammatory response to Gram-positive bacteria remains nevertheless largely unknown. In this Study we investigated the production of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (1L-1 beta) and interleukin-8 (CXCL8) in these three cell types upon stimulation with lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria that activates the pattern recognition molecule Toll-like receptor 2 (TLR2). We observed that TNF-alpha gene expression was up-regulated in all LTA-stimulated cell types. IL-1 beta gene expression was not or barely detectable in odontoblast-like cells and pulp fibroblasts when stimulated or not, but was expressed ill immature DCs and increased upon stimulation. TNF-alpha and IL-1 beta proteins were detected in DC culture supernatants but not in odontoblast-like cell and pulp fibroblast ones. CXCL8 gene and protein were clearly expressed and increased in the three cell types upon LTA stimulation. These data indicate that LTA-dependent TLR2 activation in odontoblasts and pulp fibroblasts, in contrast to immature DCs, does not lead to significant TNF-alpha and IL-1 beta production, but that all three cell types influence the pulp inflammatory/immune response through CXCL8 synthesis and secretion. (C) 2009 Elsevier GmbH. All rights reserved.